Streptococcus pyogenes (group A streptococcus or GA) is the causative agent of a number of human diseases, including pharyngitis, rheumatic fever, streptococcal toxic shock syndrome and necrotizing fasciitis. Our laboratory recently showed that mucRS is a negative regulatory of three importance virulence factor in GS. The aim of this proposal is to determine the molecular mechanisms involved in mucRS-mediated regulation of gene expression and how this relates in mucRS-mediated regulation of gene expression and how this relates to virulence in GAS. I will (i) characterize the mechanism(s) of repression of MucR, (ii) examine the role of phosphorylation of MucR, (iii) analyze the effect of MucS activity on MucR and (iv) determine the effect of a defined set of environmental conditions of MucRS activity.